Dopamine D2 receptor knockout mice develop features of Parkinson disease.

Objective: This study questions whether increased dopamine (DA) turnover in nigral neurons leads to formation of Lewy bodies (LBs), the characteristic alpha-synuclein-containing cytoplasmic inclusion of Parkinson disease (PD).

Methods: Mice with targeted deletion of the dopamine D(2) receptor gene (D(2)R[-/-]) have higher striatal and nigral dopamine turnover and elevated oxidative stress. These mice were examined for evidence of histological, biochemical, and gene expression changes consistent with a synucleinopathy.

Adult neural stem/progenitor cells reduce NMDA-induced excitotoxicity via the novel neuroprotective peptide pentinin.

Although the potential of adult neural stem cells to repair damage via cell replacement has been widely reported, the ability of endogenous stem cells to positively modulate damage is less well studied. We investigated whether medium conditioned by adult hippocampal stem/progenitor cells altered the extent of excitotoxic cell death in hippocampal slice cultures. Conditioned medium significantly reduced cell death following 24 h of exposure to 10 microM NMDA.

GDNF gene delivery via the p75(NTR) receptor rescues injured motor neurons.

The retrograde axonal transport mechanism of motor neurons has been exploited to deliver the gene encoding Glial cell line-derived neurotrophic factor (GDNF) into the central nervous system to provide trophic support following injury. A nonviral gene delivery system, consisting of a monoclonal antibody (MC192) that binds the neurotrophic receptor, p75(NTR), coupled to poly-L-lysine, was constructed and used to deliver the gene via a receptor-mediated mechanism. The MC192-poly-l-lysine/pGDNF complex was injected into the hind limb of newborn rats to allow gene expression within motor neurons prior to sciatic nerve transection.

Use of engineered peripheral nerve autografts for spinal cord repair.

We developed a clinically compatible protocol for the production of engineered tissue for grafting into the injured spinal cord. We used autologous tissue derived from pre-ligated peripheral nerves, which avoids supply, immunocompatibility and ethical hinderances, combined with non-viral transfection, which is a versatile and non-immunogenic gene transfer method. In-vitro transfection of glial cells or primary tissue from pre-ligated rat peripheral nerve with the neurotrophic gene brain-derived neurotrophic factor significantly enhanced its expression, when quantified or labelled by immunofluorescence.

Improved non-viral transfection of glial and adult neural stem cell lines and of primary astrocytes by combining agents with complementary modes of action.

Background: Rational design of gene vectors for therapeutic applications requires understanding of transfection mechanisms. In this study, multiple transfection assays revealed complementary mechanisms between two commonly used transfection agents. This finding was then exploited to produce improved transfection outcomes.